Guanine nucleotides inhibit cAMP accumulation induced by metabotropic glutamate receptor activation.
Metabotropic glutamate receptors (mGluRs) have been shown to modulate adenylate cyclase activity via G-proteins. In the present study we report similar results to the previously observed in the literature, showing that glutamate and the metabotropic agonists, 1S,3R-ACPD or quisqualate induced cAMP accumulation in hippocampal slices of young rats. Moreover, guanine nucleotides GTP, GDP or GMP, inhibited the glutamate-induced cAMP accumulation. By measuring LDH activity in the buffer surrounding the slices, we showed that the integrity of the slices was maintained, indicating that the effect of guanine nucleotides was extracellular. GMP, GDPbeta-S or Gpp(NH)p abolished quisqualate-induced cAMP accumulation. GDPbeta-S or Gpp(NH)p but not GMP inhibited 1S,3R-ACPD-induced cAMP accumulation. The response evoked by glutamate was also abolished by the mGluR antagonists: L-AP3 abolished glutamate-induced cAMP accumulation in a dose-dependent manner and MCPG was effective only at the 2 mM dose. DNQX was ineffective. We are reporting here, an inhibition induced by guanine nucleotides, via an extracellular site (s), similar to the observed with classical glutamate antagonists on a cellular response evoked by mGluR agonists.
Tasca
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CI
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, Brasil.
Cardoso
L F
LF
Martini
L H
LH
Ramírez
G
G
Souza
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DO
D000818:Animals; D000242:Cyclic AMP / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006157:Guanosine Monophosphate / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology
D006150:Guanine Nucleotides; D009498:Neurotoxins; D018094:Receptors, Metabotropic Glutamate; D013873:Thionucleotides; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D006153:Guanosine Diphosphate; D006165:Guanylyl Imidodiphosphate; D018698:Glutamic Acid; C023427:guanosine 5'-O-(2-thiodiphosphate); D006157:Guanosine Monophosphate; D006160:Guanosine Triphosphate; D016318:Quisqualic Acid; D000242:Cyclic AMP